Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures. RYGB and VSG have very different anatomical restructuring but both surgeries are effective, to varying degrees, at inducing weight loss and T2DM remission. Both weight loss-dependent and weight loss-independent alterations in multiple tissues (such as the intestine, liver, pancreas, adipose tissue and skeletal muscle) yield net improvements in insulin resistance, insulin secretion and insulin-independent glucose metabolism. In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, potentially reflecting the extreme effects of potent glucose reduction after surgery. This Review addresses the effects of bariatric surgery on glucose regulation and the potential mechanisms responsible for both the resolution of T2DM and the induction of hypoglycaemia.
Roux-en-Y gastric bypass and vertical sleeve gastrectomy are the two most widely used forms of bariatric surgery; both induce considerable weight loss and can induce remission of type 2 diabetes mellitus (T2DM) in some patients.
Bariatric surgery has important weight loss-dependent and weight loss-independent mechanisms for the induction of resolution of T2DM.
Bariatric surgery affects the glucoregulatory function of multiple target organs, including the intestine, liver, pancreas, adipose tissue and skeletal muscle.
In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, thereby representing a potential extreme example of altered glucose metabolism.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Schauer, P. R. et al. Bariatric surgery versus intensive medical therapy for diabetes — 5-year outcomes. N. Engl. J. Med. 376, 641–651 (2017). This 5-year follow-up to the STAMPEDE clinical trial randomized patients with T2DM to RYGB, VSG or medical management, and showed that RYGB and VSG were superior to medical therapy in terms of weight loss, glycaemic control and reduction in medication use.
Kirwan, J. P. et al. Diabetes remission in the alliance of randomized trials of medicine versus metabolic surgery in type 2 diabetes (ARMMS-T2D). Diabetes Care 45, 1574–1583 (2022).
Mingrone, G. et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 397, 293–304 (2021).
Pories, W. J. et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann. Surg. 215, 633–642 (1992).
Riddle, M. C. et al. Consensus report: definition and interpretation of remission in type 2 diabetes. J. Clin. Endocrinol. Metab. 44, 2438–2444 (2021).
Carlsson, L. M. et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N. Engl. J. Med. 367, 695–704 (2012).
Yoshino, M. et al. Effects of diet versus gastric bypass on metabolic function in diabetes. N. Engl. J. Med. 383, 721–753 (2020). This study examined key metabolic phenotypes related to glucose metabolism and insulin sensitivity in participants undergoing matched weight loss via surgery or dietary restriction, showing similar metabolic and physiological responses.
Dang, J. T. et al. Predictive factors for diabetes remission after bariatric surgery. Can. J. Surg. 62, 315–319 (2019).
Sjöholm, K., Sjöström, E., Carlsson, L. M. S. & Peltonen, M. Weight change-adjusted effects of gastric bypass surgery on glucose metabolism: two- and 10-year results from the Swedish obese subjects (SOS) study. Diabetes Care 39, 625–631 (2016).
Mcglone, E. et al. Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: clinical outcome and cost-effectiveness analyses. PLoS Med. 17, 5 (2020).
Nosso, G. et al. Comparative effects of Roux-en-Y gastric bypass and sleeve gastrectomy on glucose homeostasis and incretin hormones in obese type 2 diabetic patients: a one-year prospective study. Horm. Metab. Res. 48, 312–317 (2016).
Nannipieri, M. et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J. Clin. Endocrinol. Metab. 98, 4391–4399 (2013).
Keidar, A. et al. Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial. Diabetologia 56, 1914–1918 (2013).
Lee, W.-J. et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch. Surg. 146, 143–148 (2011).
Blackstone, R., Bunt, J., Celaya Cortes, M. & Sugerman, H. Type 2 diabetes after gastric bypass: remission in five models using HbA1c, fasting blood glucose, and medication status. Surg. Obes. Relat. Dis. 8, 548–555 (2012).
Zechner, J. F. et al. Weight-independent effects of Roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans. Gastroenterology 144, 580–590.e7 (2013).
Pontiroli, A. E., Gniuli, D. & Mingrone, G. Early effects of gastric banding (LGB) and of biliopancreatic diversion (BPD) on insulin sensitivity and on glucose and insulin response after OGTT. Obes. Surg. 20, 474–479 (2010).
Petrov, M. S. & Taylor, R. Intra-pancreatic fat deposition: bringing hidden fat to the fore. Nat. Rev. Gastroenterol. Hepatol. 19, 153–168 (2022).
Steven, S. et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: pathophysiological changes in responders and nonresponders. Diabetes Care 39, 808–815 (2016).
Chambers, A. P. et al. Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. AJP Endocrinol. Metab. 306, E424–E432 (2014).
Cavin, J. B. et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology 150, 454–464.e9 (2016).
Saeidi, N. et al. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341, 406–410 (2013).
Ku, C. R. et al. Intestinal glycolysis visualized by FDG PET/CT correlates with glucose decrement after gastrectomy. Diabetes 66, 385–391 (2017).
Franquet, E. et al. PET-CT reveals increased intestinal glucose uptake after gastric surgery. Surg. Obes. Relat. Dis. 15, 643–649 (2019).
Ben-Zvi, D. et al. Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species. Cell Metab. 28, 310–323.e6 (2018). This study examined the molecular changes in multiple tissues after RYGB in mice and humans, identifying key molecular responses.
Kim, K.-S. et al. Vertical sleeve gastrectomy induces enteroendocrine cell differentiation of intestinal stem cells through bile acid signaling. JCI Insight 1, e154302 (2022). This paper finds bile acid-driven increases in enteroendocrine cell differentiation in a mouse model of VSG.
Chambers, A. P. et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141, 950–958 (2011).
Yan, Y. et al. Roux-en-Y gastric bypass surgery suppresses hepatic gluconeogenesis and increases intestinal gluconeogenesis in a T2DM rat model. Obes. Surg. 26, 2683–2690 (2016).
Stefater, M. A. et al. Portal venous metabolite profiling after RYGB in male rats highlights changes in gut-liver axis. J. Endocrinol. 4, bvaa003 (2020). This paper compared the metabolomic profile of metabolites in the portal vein after RYGB in rats to sham surgery control rats.
Bozadjieva-Kramer, N. et al. Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice. Nat. Commun. 12, 4768 (2021).
Rabl, C. & Campos, G. M. The impact of bariatric surgery on nonalcoholic steatohepatitis. Semin. Liver Dis. 32, 80–91 (2012).
Whang, E. et al. Vertical sleeve gastrectomy attenuates the progression of non-alcoholic steatohepatitis in mice on a high-fat high-cholesterol diet. Obes. Surg. 29, 2420–2429 (2019).
Verbeek, J. et al. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut 64, 673–683 (2015).
Romero-Gómez, M., Zelber-Sagi, S. & Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 67, 829–846 (2017).
Myronovych, A. et al. The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice. Obesity 22, 2301–2311 (2014).
Ben-Haroush Schyr, R. et al. Sleeve gastrectomy suppresses hepatic glucose production and increases hepatic insulin clearance independent of weight loss. Diabetes 70, 2289–2298 (2021).
Mazzini, G. S. et al. Gastric bypass increases circulating bile acids and activates hepatic farnesoid X receptor (FXR) but requires intact peroxisome proliferator activator receptor alpha (PPARα) signaling to significantly reduce liver fat content. J. Gastrointest. Surg. 25, 871–879 (2021).
Grayson, B. E. et al. Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling. Biol. Sex Differ. 8, 4 (2017).
Klein, S. et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 130, 1564–1572 (2006).
Hankir, M. K. et al. Gastric bypass surgery recruits a gut PPAR-α-striatal D1R pathway to reduce fat appetite in obese rats. Cell Metab. 25, 335–344 (2017).
Hutch, C. R. et al. Oea signaling pathways and the metabolic benefits of vertical sleeve gastrectomy. Ann. Surg. 271, 509–518 (2020).
Karthickeyan, C. K., Mehrabian, M. & Lusis, A. J. Sex differences in metabolism and cardiometabolic disorders. Curr. Opin. Lipidol. 29, 404–410 (2018).
Hutch, C. R. et al. Diet-dependent sex differences in the response to vertical sleeve gastrectomy. Am. J. Physiol. Endocrinol. Metab. 321, E11–E23 (2021).
Bhatia, H., Pattnaik, B. R. & Datta, M. Inhibition of mitochondrial β-oxidation by miR-107 promotes hepatic lipid accumulation and impairs glucose tolerance in vivo. Int. J. Obes. 40, 861–869 (2016).
Bhatia, H., Verma, G. & Datta, M. MiR-107 orchestrates ER stress induction and lipid accumulation by post-transcriptional regulation of fatty acid synthase in hepatocytes. Biochim. Biophys. Acta Gene Regul. Mech. 1839, 334–343 (2014).
Kornfeld, J. W. et al. Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature 494, 111–115 (2013).
Trajkovski, M. et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 474, 649–653 (2011).
Gancheva, S. et al. Dynamic changes of muscle insulin sensitivity after metabolic surgery. Nat. Commun. 10, 4179 (2019).
Angelini, G. et al. Small intestinal metabolism is central to whole-body insulin resistance. Gut 70, 1098–1109 (1098).
Salinari, S. et al. Insulin sensitivity and secretion changes after gastric bypass in normotolerant and diabetic obese subjects. Ann. Surg. 257, 462–468 (2013).
Dirksen, C. et al. Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass. Diabetologia 56, 2679–2687 (2013).
Garibay, D. et al. β-Cell glucagon-like peptide-1 receptor contributes to improved glucose tolerance after vertical sleeve gastrectomy. Endocrinology 157, 3405–3409 (2016).
Salehi, M., Gastaldelli, A. & Defronzo, R. Prandial hepatic glucose production during hypoglycemia is altered after gastric bypass surgery and sleeve gastrectomy. Metabolism 131, 155199 (2022).
Svane, M. S. et al. Postprandial nutrient handling and gastrointestinal hormone secretion after Roux-en-Y Gastric bypass vs sleeve gastrectomy. Gastroenterology 156, 1627–1641.e1 (2019).
Ferrannini, E. & Mingrone, G. Impact of different bariatric surgical procedures on insulin action and β-cell function in type 2 diabetes. Diabetes Care 32, 514–520 (2009).
Akalestou, E. et al. Intravital imaging of islet Ca2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice. Nat. Commun. 12, 5165 (2021).
Oppenländer, L. et al. Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes. Mol. Metab. 54, 101330 (2021).
Talchai, C., Xuan, S., Lin, H. V., Sussel, L. & Accili, D. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell 150, 1223–1234 (2012).
Qian, B. et al. Reduction of pancreatic β-cell dedifferentiation after gastric bypass surgery in diabetic rats. J. Mol. Cell Biol. 6, 531–534 (2014).
Abu-Gazala, S. et al. Sleeve gastrectomy improves glycemia independent of weight loss by restoring hepatic insulin sensitivity. Diabetes 67, 1079–1085 (2018).
Li, F. et al. Preventative sleeve gastrectomy contributes to maintaining β cell function in db/db diabetic mouse. Obes. Surg. 26, 2402–2410 (2016).
Mosinski, J. D. et al. Roux-en-Y gastric bypass restores islet function and morphology independent of body weight in ZDF rats. Am. J. Physiol. Endocrinol. Metab. 320, E392–E398 (2021).
Zhu, C., Xu, R., Li, Y., Andrade, M. & Yin, D. P. Gastric bypass prevents diabetes in genetically modified mice and chemically induced diabetic mice. PLoS One 16, e0258942 (2021).
Kim, K.-S. & Sandoval, D. A. Endocrine function after bariatric surgery. Compr. Physiol. 7, 783–798 (2017).
Casajoana, A. et al. Predictive value of gut peptides in T2D remission: randomized controlled trial comparing metabolic gastric bypass, sleeve gastrectomy and greater curvature plication. Obes. Surg. 27, 2235–2245 (2017).
Jacobsen, S. H. et al. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obes. Surg. 22, 1084–1096 (2012).
Korner, J. et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity 14, 1553–1561 (2006).
Shin, A. C., Zheng, H., Townsend, R. L., Sigalet, D. L. & Berthoud, H.-R. R. Meal-induced hormone responses in a rat model of Roux-en-Y gastric bypass surgery. Endocrinology 151, 1588–1597 (2010).
Yousseif, A. et al. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes. Surg. 24, 241–252 (2014).
McLaughlin, T., Peck, M., Holst, J. & Deacon, C. Reversible hyperinsulinemic hypoglycemia after gastric bypass: a consequence of altered nutrient delivery. J. Clin. Endocrinol. Metab. 95, 1851–1855 (2010).
Thomas, C. et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10, 167–177 (2009).
Ding, L. et al. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology 64, 760–773 (2016).
McGavigan, A. K. et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut 66, 226–234 (2017).
Nausheen, S., Shah, I. H., Pezeshki, A., Sigalet, D. L. & Chelikani, P. K. Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats. AJP Endocrinol. Metab. 305, E507–E518 (2013).
Li, F., Peng, Y., Zhang, M., Yang, P. & Qu, S. Sleeve gastrectomy activates the GLP-1 pathway in pancreatic β cells and promotes GLP-1-expressing cells differentiation in the intestinal tract. Mol. Cell. Endocrinol. 436, 33–40 (2016).
Wilson-Pérez, H. E. et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide-1 receptor deficiency. Diabetes 62, 2380–2385 (2013).
Mokadem, M., Zechner, J. F., Margolskee, R. F., Drucker, D. J. & Aguirre, V. Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency. Mol. Metab. 3, 191–201 (2014).
Kim, K.-S. et al. Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy. JCI Insight 4, e129452 (2019).
Shaham, O. et al. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol. Syst. Biol. 4, 214 (2008).
Evers, S. S., Sandoval, D. A. & Seeley, R. J. The physiology and molecular underpinnings of the effects of bariatric surgery on obesity and diabetes. Annu. Rev. Physiol. 79, 313–334 (2017).
Patti, M.-E. E. et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity 17, 1671–1677 (2009).
Ryan, K. K. et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509, 183–188 (2014).
Myronovych, A. et al. Assessment of the role of FGF15 in mediating the metabolic outcomes of murine vertical sleeve gastrectomy (VSG). Am. J. Physiol. Gastrointest. Liver Physiol. 319, G669–G684 (2020).
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F. & Staels, B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev. 89, 147–191 (2009).
Watanabe, M. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439, 484–489 (2006).
Thomas, C., Auwerx, J. & Schoonjans, K. Bile acids and the membrane bile acid receptor TGR5-connecting nutrition and metabolism. Thyroid 18, 167–174 (2008).
Cicione, C., Degirolamo, C. & Moschetta, A. Emerging role of fibroblast growth factors 15/19 and 21 as metabolic integrators in the liver. Hepatology 56, 2404–2411 (2012).
Haluzíková, D. et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity 21, 1335–1342 (2013).
Sachdev, S. et al. FGF 19 and bile acids increase following Roux-en-Y gastric bypass but not after medical management in patients with type 2 diabetes. Obes. Surg. 26, 957–965 (2015).
Mulla, C. M. et al. Plasma FGF-19 levels are increased in patients with post-bariatric hypoglycemia. Obes. Surg. 29, 2092–2099 (2019).
Hao, Z. et al. Roux-en-Y gastric bypass surgery-induced weight loss and metabolic improvements are similar in TGR5-deficient and wildtype mice. Obes. Surg. 28, 3227–3236 (2018).
Dreyfuss, J. M. et al. High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control. Nat. Commun. 12, 6951 (2021). This study utilized fasting plasma samples obtained longitudinally from patients with T2DM randomized to RYGB or medical management, showing RYGB-associated progressive increases in multiple bile acid species and FGF19, and reductions in branched-chain amino acid-related metabolites over time.
van den Broek, M. et al. Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery. Int. J. Obes. 45, 619–630 (2021).
Chaudhari, S. N. et al. Bariatric surgery reveals a gut-restricted TGR5 agonist with anti-diabetic effects. Nat. Chem. Biol. 17, 20–29 (2021).
White, P. J. & Newgard, C. B. Branched-chain amino acids in disease. Science 363, 582–583 (2019).
Laferrère, B. et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci. Transl. Med. 3, 80re2 (2011).
Tremaroli, V. et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 22, 228–238 (2015).
Fouladi, F. et al. The role of the gut microbiota in sustained weight loss following Roux-en-Y gastric bypass surgery. Obes. Surg. 29, 1259–1267 (2019).
Dang, J. T. et al. Ileal microbial shifts after Roux-en-Y gastric bypass orchestrate changes in glucose metabolism through modulation of bile acids and L-cell adaptation. Sci. Rep. 11, 23813 (2021).
Debédat, J. et al. The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass. Gut Microbes 14, 2050635 (2022).
Simonson, D. C., Halperin, F., Foster, K., Vernon, A. & Goldfine, A. B. Clinical and patient-centered outcomes in obese patients with type 2 diabetes 3 years after randomization to Roux-en-Y gastric bypass surgery versus intensive lifestyle management: the SLIMM-T2D study. Diabetes Care 41, 670–679 (2018).
Faramia, J. et al. IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery. Cell Rep. Med. 2, 100248 (2021).
Kim, K.-S., Seeley, R. J. & Sandoval, D. A. Signalling from the periphery to the brain that regulates energy homeostasis. Nat. Rev. Neurosci. 19, 185–196 (2018).
Martinou, E., Stefanova, I., Iosif, E. & Angelidi, A. M. Neurohormonal changes in the gut-brain axis and underlying neuroendocrine mechanisms following bariatric surgery. Int. J. Mol. Sci. 23, 1–40 (2022).
Bethea, M. & Sandoval, D. A. Gut factors mediating the physiological impact of bariatric surgery. Curr. Diab. Rep. 22, 371–383 (2022).
Müller, T. D. et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 30, 72–130 (2019).
Rosario, W. et al. The brain-to-pancreatic islet neuronal map reveals differential glucose regulation from distinct hypothalamic regions. Diabetes 65, 2711–2723 (2016).
Shin, A. C., Zheng, H. & Berthoud, H.-R. Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism. Ann. Surg. 255, 294–301 (2012).
Okafor, P. et al. Effect of vagotomy during Roux-en-Y gastric bypass surgery on weight loss outcomes. Obes. Res. Clin. Pract. 9, 274–280 (2015).
Hao, Z. et al. Vagal innervation of intestine contributes to weight loss after Roux-en-Y gastric bypass surgery in rats. Obes. Surg. 24, 2145–2151 (2014).
Salehi, M., Vella, A., Mclaughlin, T. & Patti, M., Society, E. Hypoglycemia after gastric bypass surgery: current concepts and controversies. J. Clin. Endocrinol. Metab. 103, 2815–2826 (2018). This review summarizes the pathophysiology, diagnosis and treatment of PBH.
Capristo, E. et al. Incidence of hypoglycemia after gastric bypass versus sleeve gastrectomy: a randomized trial. J. Clin. Endocrinol. Metab. 103, 2136–2146 (2018).
Lazar, L. O. et al. Symptomatic and asymptomatic hypoglycemia post three different bariatric procedures: a common and severe complication. Endocr. Pract. https://doi.org/10.4158/EP-2019-0185 (2019).
Lee, C. J. et al. Comparison of hormonal response to a mixed meal challenge in hypoglycemia after sleeve gastrectomy versus gastric bypass. J. Clin. Endocrinol. Metab. 107, e4159–e4166 (2022).
Abrahamsson, N., Engströ, B. E., Sundbom, M. &Karlsson, F. A. Hypoglycemia in everyday life after gastric bypass and duodenal switch. Eur. J. Endocrinol. 173, 91–100 (2015).
Kubota, T. et al. Utility of continuous glucose monitoring following gastrectomy. Gastric Cancer 23, 699–706 (2020).
Zaloga, G. P. & Chernow, B. Postprandial hypoglycemia after Nissen fundoplication for reflux esophagitis. Gastroenterology 84, 840–842 (1983).
Bairdain, S. et al. Laparoscopic adjustable gastric banding and hypoglycemia. Case Rep. Endocrinol. 2013, 671848 (2013).
Sessa, L. et al. Effect of single anastomosis duodenal-ileal bypass with sleeve gastrectomy on glucose tolerance test: comparison with other bariatric procedures. Surg. Obes. Relat. Dis. 15, 1091–1097 (2019).
Marsk, R., Jonas, E., Rasmussen, F. & Näslund, E. Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden. Diabetologia 53, 2307–2311 (2010).
Lee, C. J., Brown, T. T., Schweitzer, M., Magnuson, T. & Clark, J. M. The incidence and risk factors associated with developing symptoms of hypoglycemia after bariatric surgery. Surg. Obes. Relat. Dis. 14, 797–802 (2018).
Fischer, L. E. et al. Postbariatric hypoglycemia: symptom patterns and associated risk factors in the Longitudinal Assessment of Bariatric Surgery study. Surg. Obes. Relat. Dis. 17, 1787–1798 (2021). This longitudinal cohort study examined hypoglycaemia symptoms following RYGB and laparoscopic adjustable gastric banding to identify risk factors for PBH.
Kefurt, R. et al. Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test. Surg. Obes. Relat. Dis. 11, 564–569 (2015). This study utilized CGM to evaluate hypoglycaemia in 40 individuals post-RYGB, showing asymptomatic low sensor glucose levels (<55 mg/dl) in 75% of the patients and nocturnal hypoglycaemia in 38%.
Salehi, M., Gastaldelli, A. & D’Alessio, D. A. Altered islet function and insulin clearance cause hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia. J. Clin. Endocrinol. Metab. 99, 2008–2017 (2014).
Goldfine, A. B. et al. Patients with Neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J. Clin. Endocrinol. Metab. 92, 4678–4685 (2007).
Salehi, M., Gastaldelli, A. & D’Alessio, D. A. Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass. Gastroenterology 146, 669–680.e2 (2014).
Lee, D. et al. Glycemic patterns are distinct in post-bariatric hypoglycemia after gastric bypass (PBH-RYGB). J. Clin. Endocrinol. Metab. 106, 2291–2303 (2021).
van Furth, A. M. et al. Cholecystectomy increases the risk of dumping syndrome and postbariatric hypoglycemia after bariatric surgery. Surg. Obes. Relat. Dis. 16, 1939–1947 (2020).
Lee, C. J. et al. Risk of post-gastric bypass surgery hypoglycemia in nondiabetic individuals: a single center experience. Obesity 24, 1342–1348 (2016).
Rebelos, E. et al. Impact of postprandial hypoglycemia on weight loss after bariatric surgery. Obes. Surg. 30, 2266–2273 (2020).
Tharakan, G. et al. Roles of increased glycaemic variability, GLP-1 and glucagon in hypoglycaemia after Roux-en-Y gastric bypass. Eur. J. Endocrinol. 177, 455–464 (2017).
Evers, S. S. et al. Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats. Mol. Metab. 32, 148–159 (2020).
Abegg, K. et al. Effect of bariatric surgery combined with medical therapy versus intensive medical therapy or calorie restriction and weight loss on glycemic control in Zucker diabetic fatty rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, 321–329 (2015).
Hepprich, M. et al. Postprandial hypoglycemia in patients after gastric bypass surgery is mediated by glucose-induced IL-1β. Cell Metab. 31, 699–709 (2020).
Vanderveen, K. A. et al. Outcomes and quality of life after partial pancreatectomy for noninsulinoma pancreatogenous hypoglycemia from diffuse islet cell disease. Surgery 148, 1237–1245 (2010).
Meier, J. J., Butler, A. E., Galasso, R. & Butler, P. C. Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased -cell turnover. Diabetes Care 29, 1554–1559 (2006).
Craig, C. M., Liu, L.-F., Deacon, C. F., Holst, J. J. & McLaughlin, T. L. Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia. Diabetologia 60, 531–540 (2017).
Patti, M. E., Li, P. & Goldfine, A. B. Insulin response to oral stimuli and glucose effectiveness increased in neuroglycopenia following gastric bypass. Obesity 23, 798–807 (2015).
Øhrstrøm, C. C. et al. Counterregulatory responses to postprandial hypoglycemia after Roux-en-Y gastric bypass. Surg. Obes. Relat. Dis. 17, 55–63 (2021). This study evaluated counterregulatory responses during postprandial hypoglycaemia in individuals with PBH who underwent RYGB.
Mulla, C. M. et al. A randomized, placebo-controlled double-blind trial of a closed-loop glucagon system for postbariatric hypoglycemia. J. Clin. Endocrinol. Metab. 105, 1260–1271 (2020).
Nakhaee, S. et al. The effect of tramadol on blood glucose concentrations: a systematic review. Expert Rev. Clin. Pharmacol. 13, 531–543 (2020).
Mulla, C. M. et al. Insulinoma after bariatric surgery: diagnostic dilemma and therapeutic approaches. Obes. Surg. 26, 874–881 (2016).
Zanley, E. et al. Guidelines for gastrostomy tube placement and enteral nutrition in patients with severe, refractory hypoglycemia after gastric bypass. Surg. Obes. Relat. Dis. 17, 456–465 (2021).
Davis, D. B. et al. Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal: confirming a non-pancreatic etiology. Mol. Metab. 9, 15–27 (2018).
M.E.P. reports personal consulting fees from Astra Zeneca, Fractyl, Hanmi Pharmaceutical, MBX Biosciences, Recordati, Poxel, Eiger Pharmaceuticals, and Xeris and grants from Chan-Zuckerberg Initiative, Dexcom and Helmsley Trust, outside the submitted work. D.A.S. reports consulting fees from Metis Therapeutics, outside the submitted work.
Peer review information
Nature Reviews Endocrinology thanks Geltrude Mingrone, Alex Miras, Pirjo Nuutila and Antonio Ettore Pontiroli for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Sandoval, D.A., Patti, M.E. Glucose metabolism after bariatric surgery: implications for T2DM remission and hypoglycaemia. Nat Rev Endocrinol (2022). https://doi.org/10.1038/s41574-022-00757-5